Coagentus Pharma, LLC

Before any potential new medicine can be discovered, scientists work to understand the disease to be treated as well as possible and to unravel the underlying cause of the condition. They try to understand how the genes are altered, how that affects the proteins they encode and how those proteins interact with each other in living cells, how those affected cells change the specific tissue they are in and finally how the disease affects the entire patient. This knowledge is the basis for treating the problem. Researchers from government, academia and industry all contribute to this knowledge base. However, even with new tools and insights, this research takes many years of work and, too often, leads to frustrating dead ends. And even if the research is successful, it will take many more years of work to turn this basic understanding of what causes a disease into a new treatment﻿.

DRUG DISCOVERY

Armed with their understanding of the disease, scientists are ready to begin looking for a drug. They search for a molecule, or “lead compound,” that may act on their target to alter the disease course. If successful over long odds and years of testing, the lead compound can ultimately become a new medicine. There are a few ways to find a lead compound:

Nature: Until recently, scientists usually turned to nature to find interesting compounds for fighting disease. Bacteria found in soil and moldy plants both led to important new treatments, for example. Nature still offers many useful substances, but now there are other ways to approach drug discovery.

De novo: Thanks to advances in chemistry, scientists can also create molecules from scratch. They can use sophisticated computer modeling to predict what type of molecule may work.

High-throughput Screening: This process is the most common way that leads are usually found. Advances in robotics and computational power allow researchers to test hundreds of thousands of compounds against the target to identify any that might be promising. Based on the results, several lead compounds are usually selected for further study.

PRECLINICAL DEVELOPMENT

With one or more optimized compounds in hand, researchers turn their attention to testing them extensively to determine if they should move on to testing in humans. Scientists carry out in vitro and in vivo tests. In vitro tests are experiments conducted in the lab, usually carried out in test tubes and beakers (“vitro” is “glass” in Latin) and in vivo studies are those in living cell cultures and animal models (“vivo” is “life” in Latin). Scientists try to understand how the drug works and what its safety profile looks like. The U.S. Food and Drug Administration (FDA) requires extremely thorough testing before the candidate drug can be studied in humans. During this stage researchers also must work out how to make large enough quantities of the drug for clinical trials. Techniques for making a drug in the lab on a small scale do not translate easily to larger production. This is the first scale up. The drug will need to be scaled up even more if it is approved for use in the general patient population. At the end of several years of intensive work, the discovery phase concludes. After starting with approximately 5,000 to 10,000 compounds, scientists now have winnowed the group down to between one and five molecules, “candidate drugs,” which will be studied in clinical trials.﻿

INVESTIGATIONAL NEW DRUG (IND) APPLICATION AND SAFETY

Before any clinical trial can begin, the researchers must file an Investigational New Drug (IND) application with the FDA. The application includes the results of the preclinical work, the candidate drug’s chemical structure and how it is thought to work in the body, a listing of any side effects and manufacturing information. The IND also provides a detailed clinical trial plan that outlines how, where and by whom the studies will be performed. The FDA reviews the application to make sure people participating in the clinical trials will not be exposed to unreasonable risks. In addition to the IND application, all clinical trials must be reviewed and approved by the Institutional Review Board (IRB) at the institutions where the trials will take place. This process includes the development of appropriate informed consent, which will be required of all clinical trial participants. Statisticians and others are constantly monitoring the data as it becomes available. The FDA or the sponsor company can stop the trial at any time if problems arise. In some cases a study may be stopped because the candidate drug is performing so well that it would be unethical to withhold it from the patients receiving a placebo or another drug. Finally, the company sponsoring the research must provide comprehensive regular reports to the FDA and the IRB on the progress of clinical trials.﻿